Educational inequalities in multimorbidity at older ages: a multi-generational population-based study.

BACKGROUND: Social inequalities in multimorbidity may occur due to familial and/or individual factors and may differ between men and women. Using population-based multi-generational data, this study aimed to (1) assess the roles of parental and individual education in the risk of multimorbidity and (2) examine the potential effect modification by sex. METHODS: Data were analysed from 62 060 adults aged 50+ who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 European countries. Intergenerational educational trajectories (exposure) were High-High (reference), Low-High, High-Low and Low-Low, corresponding to parental-individual educational attainments. Multimorbidity (outcome) was ascertained between 2013 and 2020 as self-reported occurrence of ≥2 diagnosed chronic conditions. Inequalities were quantified as multimorbidity-free years lost (MFYL) between the ages of 50 and 90 and estimated via differences in the area under the standardized cumulative risk curves. Effect modification by sex was assessed via stratification. RESULTS: Low individual education was associated with higher multimorbidity risk regardless of parental education. Compared to the High-High trajectory, Low-High was associated with -0.2 MFYL (95% confidence intervals: -0.5 to 0.1), High-Low with 3.0 (2.4-3.5), and Low-Low with 2.6 (2.3-2.9) MFYL. This pattern was observed for both sexes, with a greater magnitude for women. This effect modification was not observed when only diseases diagnosed independently of healthcare-seeking behaviours were examined. CONCLUSIONS: Individual education was the main contributor to intergenerational inequalities in multimorbidity risk among older European adults. These findings support the importance of achieving a high education to mitigate multimorbidity risk.

Cardiovascular mortality trends in Switzerland 1995-2018.

Mortality rates due to coronary heart disease (CHD) and stroke have declined in the last century in high-income countries, including Switzerland. However, these rates have plateaued in several countries. We assessed CHD and stroke mortality trends (1995-2018) in Switzerland. We estimated annual rate changes via JoinPoint regression. Rates decreased steadily in most sex and age groups; however, in those aged 60-74, stroke rates plateaued after 2012 among men and CHD rates plateaued after 2015 among women. Cardiovascular mortality continues to decrease in most of the Swiss population. Prevention efforts should be maintained, especially in individuals aged 60-74.

Life-course socioeconomic disadvantage and lung function: a multicohort study of 70 496 individuals.

BACKGROUND: Lung function is an important predictor of health and a marker of physical functioning at older ages. This study aimed to quantify the years of lung function lost according to disadvantaged socioeconomic conditions across the life-course. METHODS: This multicohort study used harmonised individual-level data from six European cohorts with information on life-course socioeconomic disadvantage and lung function assessed by forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). 70 496 participants (51% female) aged 18-93 years were included. Socioeconomic disadvantage was measured in early life (low paternal occupational position), early adulthood (low educational level) and adulthood (low occupational position). Risk factors for poor lung function (e.g. smoking, obesity, sedentary behaviour, cardiovascular and respiratory diseases) were included as potential mediators. The years of lung function lost due to socioeconomic disadvantage were computed at each life stage. RESULTS: Socioeconomic disadvantage during the life-course was associated with a lower FEV1. By the age of 45 years, individuals experiencing disadvantaged socioeconomic conditions had lost 4-5 years of healthy lung function versus their more advantaged counterparts (low educational level -4.36 (95% CI -7.33--2.37) for males and -5.14 (-10.32--2.71) for females; low occupational position -5.62 (-7.98--4.90) for males and -4.32 (-13.31--2.27) for females), after accounting for the risk factors for lung function. By the ages of 65 years and 85 years, the years of lung function lost due to socioeconomic disadvantage decreased by 2-4 years, depending on the socioeconomic indicator. Sensitivity analysis using FVC yielded similar results to those using FEV1. CONCLUSION: Life-course socioeconomic disadvantage is associated with lower lung function and predicts a significant number of years of lung function loss in adulthood and at older ages.

Differential regulation of RNA polymerase III genes during liver regeneration.

Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III transcription. Our results broadly define a class of genes close to H3K4me3 and Pol II peaks, whose Pol III occupancy is high and stable, and another class, distant from Pol II peaks, whose Pol III occupancy strongly increases after partial hepatectomy. Pol III regulation in the liver thus entails both highly expressed housekeeping genes and genes whose expression can adapt to increased demand.

[How the life course perspective transforms epidemiology]. / Comment la perspective des parcours de vie transforme l'épidémiologie.

The life course epidemiology is an interdisciplinary approach to health resulting from the convergence of centres of interest in social epidemiology, natural sciences (biology, genetics) and social sciences (psychology, sociology, history). It examines the origin of chronic diseases in the past of individuals, considering the duration and timing of exposure to different risk factors, throughout the life of the individual, from gestation to an advanced age. The life course epidemiology is interested as much in bio-psycho-social determinants as in environmental and societal influences on the trajectories of health and various diseases, either somatic or psychic.

La perspective dite des parcours de vie en épidémiologie (life course epidemiology) est une approche interdisciplinaire de la santé fruit de la convergence de l'épidémiologie sociale, des sciences naturelles (biologie, génétique) et des sciences sociales (psychologie, sociologie, histoire). Elle invite à considérer l'origine des maladies chroniques dans le passé des individus, en tenant compte de la durée et du timing de l'exposition à différents facteurs de risque, ceci tout au long de la vie de l'individu, de la gestation à un âge avancé. Dans cette perspective des parcours de vie, l'épidémiologie s'intéresse autant aux déterminants bio-psychosociaux qu'aux influences environnementales et sociétales sur les trajectoires de santé et de différentes maladies tant somatiques que psychiques.

Social inequalities in sleep-disordered breathing: Evidence from the CoLaus|HypnoLaus study.

Sleep-disordered breathing is a common condition, related to a higher cardiometabolic and neurocognitive risk. The main risk factors for sleep-disordered breathing include obesity, craniofacial characteristics, male sex and age. However, some studies have suggested that adverse socioeconomic circumstances and lifestyle-related behaviours such as smoking and alcohol use, may also be risk factors for sleep-disordered breathing. Here, we investigate the associations between socioeconomic status and sleep-disordered breathing, as measured by sleep apnea-hypopnea and oxygen desaturation indexes. Furthermore, we assess whether these associations are explained by lifestyle-related factors (smoking, sedentary behaviour, alcohol use and body mass index [BMI]). We used data from the CoLaus|HypnoLaus study, a population-based study including 2162 participants from Lausanne (Switzerland). Socioeconomic status was measured through occupation and education. Sleep-disordered breathing was assessed through polysomnography and measured using the apnea-hypopnea index (AHI: number of apnea/hypopnea events/hr: ≥15/≥30 events), and the ≥3% oxygen desaturation index (ODI: number of oxygen desaturation events/hr: ≥15/≥30 events). Lower occupation and education were associated with higher AHI and ODI (occupation: AHI30, odds ratio (OR) = 1.88, 95% confidence interval (CI) [1.07; 3.31]; ODI30, OR = 2.29, 95% CI [1.19; 4.39]; education: AHI30, OR = 1.21, 95% CI [0.85; 1.72]; ODI30, OR = 1.26, 95% CI [0.83; 1.91]). BMI was associated with socioeconomic status and AHI/ODI, and contributed to the socioeconomic gradient in SDB, with mediation estimates ranging between 43% and 78%. In this Swiss population-based study, we found that low socioeconomic status is a risk factor for sleep-disordered breathing, and that these associations are partly explained by BMI. These findings provide a better understanding of the mechanisms underlying social differences in sleep-disordered breathing and may help implement policies for identifying high-risk profiles for this disorder.

Socioeconomic status and the 25 × 25 risk factors as determinants of premature mortality: a multicohort study and meta-analysis of 1·7 million men and women.

BACKGROUND: In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors. METHODS: We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors. FINDINGS: During 26·6 million person-years at risk (mean follow-up 13·3 years [SD 6·4 years]), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98-1·11) for obesity in men and 2 ·17 (2·06-2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38-1·45 for men; 1·34, 1·28-1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21-1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking. INTERPRETATION: Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality. FUNDING: European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.

Weakened functional connectivity in patients with psychogenic non-epileptic seizures (PNES) converges on basal ganglia.

BACKGROUND: Psychogenic non-epileptic seizures (PNES) are involuntary paroxysmal events that are unaccompanied by epileptiform EEG discharges. We hypothesised that PNES are a disorder of distributed brain networks resulting from their functional disconnection.The disconnection may underlie a dissociation mechanism that weakens the influence of unconsciously presented traumatising information but exerts maladaptive effects leading to episodic failures of behavioural control manifested by psychogenic 'seizures'. METHODS: To test this hypothesis, we compared functional connectivity (FC) derived from resting state high-density EEGs of 18 patients with PNES and 18 age-matched and gender-matched controls. To this end, the EEGs were transformed into source space using the local autoregressive average inverse solution. FC was estimated with a multivariate measure of lagged synchronisation in the θ, α and ß frequency bands for 66 brain sites clustered into 18 regions. A multiple comparison permutation test was applied to deduce significant between-group differences in inter-regional and intraregional FC. RESULTS: The significant effect of PNES-a decrease in lagged FC between the basal ganglia and limbic, prefrontal, temporal, parietal and occipital regions-was found in the α band. CONCLUSION: We believe that this finding reveals a possible neurobiological substrate of PNES, which explains both attenuation of the effect of potentially disturbing mental representations and the occurrence of PNES episodes. By improving understanding of the aetiology of this condition, our results suggest a potential refinement of diagnostic criteria and management principles.

Life course epidemiology and public health.

Life course epidemiology aims to study the effect of exposures on health outcomes across the life course from a social, behavioural, and biological perspective. In this Review, we describe how life course epidemiology changes the way the causes of chronic diseases are understood, with the example of hypertension, breast cancer, and dementia, and how it guides prevention strategies. Life course epidemiology uses complex methods for the analysis of longitudinal, ideally population-based, observational data and takes advantage of new approaches for causal inference. It informs primordial prevention, the prevention of exposure to risk factors, from an eco-social and life course perspective in which health and disease are conceived as the results of complex interactions between biological endowment, health behaviours, social networks, family influences, and socioeconomic conditions across the life course. More broadly, life course epidemiology guides population-based and high-risk prevention strategies for chronic diseases from the prenatal period to old age, contributing to evidence-based and data-informed public health actions. In this Review, we assess the contribution of life course epidemiology to public health and reflect on current and future challenges for this field and its integration into policy making.

Does the effect of adolescent health behaviours on adult cardiometabolic health differ by socioeconomic background? Protocol for a population-based cohort study.

INTRODUCTION: Adolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical activity, have differential effects across socioeconomic strata. Adopting a life-course perspective and a causal inference framework, we aim to assess whether the effects of adolescent health behaviours on adult cardiometabolic health differ by levels of neighbourhood deprivation, parental education and occupational class. Gaining a better understanding of these social disparities in susceptibility to health behaviours can inform policy initiatives that aim to improve population health and reduce socioeconomic inequalities in cardiometabolic health. METHODS AND ANALYSIS: We will conduct a secondary analysis of the Young Finns Study, which is a longitudinal population-based cohort study. We will use measures of health behaviours-smoking, alcohol use, fruit and vegetable consumption, and physical activity-as exposure and parental education, occupational class and neighbourhood deprivation as effect modifiers during adolescence (ages 12-18 years). Eight biomarkers of cardiometabolic health (outcomes)-waist circumference, body mass index, blood pressure, low-density lipoprotein cholesterol, apolipoprotein B, plasma glucose and insulin resistance-will be measured when participants were aged 33-40. A descriptive analysis will investigate the clustering of health behaviours. Informed by this, we will conduct a causal analysis to estimate effects of single or clustered adolescent health behaviours on cardiometabolic health conditional on socioeconomic background. This analysis will be based on a causal model implemented via a directed acyclic graph and inverse probability-weighted marginal structural models to estimate effect modification. ETHICS AND DISSEMINATION: The Young Finns study was conducted according to the guidelines of the Declaration of Helsinki, and the protocol was approved by ethics committees of University of Helsinki, Kuopio, Oulu, Tampere and Turku. We will disseminate findings at international conferences and a manuscript in an open-access peer-reviewed journal.

Effect of dairy consumption on cognition in older adults: A population-based cohort study.

OBJECTIVE: We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy. DESIGN: Secondary analysis of a prospective population-based cohort study. PARTICIPANTS: We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland. MEASUREMENTS: The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes. METHODS: Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up. RESULTS: Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (-3% to 26.5%)] and eggs [18% (2.3%-33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes. CONCLUSION: We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results.

Intergenerational educational trajectories and inequalities in longevity: A population-based study of adults born before 1965 in 14 European countries.

Background: While educational gradients in longevity have been observed consistently in adult Europeans, these inequalities have been understudied within the context of family- and country-level influences. We utilized population-based multi-generational multi-country data to assess the role (1) of parental and individual education in shaping intergenerational inequalities in longevity, and (2) of country-level social net expenditure in mitigating these inequalities. Methods: We analyzed data from 52,271 adults born before 1965 who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 countries. Mortality from all causes (outcome) was ascertained between 2013 and 2020. Educational trajectories (exposure) were High-High (reference), Low-High, High-Low, and Low-Low, corresponding to the sequence of parental-individual educational attainment. We quantified inequalities as years of life lost (YLL) between the ages of 50 and 90 estimated via differences in the area under standardized survival curves. We assessed the association between country-level social net expenditure and YLL via meta-regression. Results: Inequalities in longevity due to educational trajectories were associated with low individual education regardless of parental education. Compared to High-High, having High-Low and Low-Low led to 2.2 (95% confidence intervals: 1.0 to 3.5) and 2.9 (2.2 to 3.6) YLL, while YLL for Low-High were 0.4 (-0.2 to 0.9). A 1% increase in social net expenditure led to an increase of 0.01 (-0.3 to 0.3) YLL for Low-High, 0.007 (-0.1 to 0.2) YLL for High-Low, and a decrease of 0.02 (-0.1 to 0.2) YLL for Low-Low. Conclusion: In European countries, individual education could be the main driver of inequalities in longevity for adults older than 50 years of age and born before 1965. Further, higher social expenditure is not associated with smaller educational inequalities in longevity.

Overcrowded housing during adolescence and future risk of premature mortality: a 28-year follow-up of 556,191 adolescents from Switzerland.

Background: Few large-scale studies have examined the health impacts of overcrowded housing in European countries. The aim of this study was to assess whether household crowding during adolescence increases the risk of all-cause and cause-specific mortality in Switzerland. Methods: Study participants were 556,191 adolescents aged 10-19 years at the 1990 census from the Swiss National Cohort. Household crowding at baseline was measured as the ratio between the number of persons living in the household and the number of available rooms, categorized as none (ratio ≤ 1), moderate (1 < ratio ≤ 1.5), and severe (ratio > 1.5). Participants were linked to administrative mortality records through 2018 and followed for premature mortality from all causes, cardiometabolic disease and self-harm or substance use. Cumulative risk differences between ages 10 and 45 were standardized by parental occupation, residential area, permit status and household type. Findings: Of the sample, 19% lived in moderately and 5% lived in severely crowded households. During an average follow-up of 23 years, 9766 participants died. Cumulative risk of death from all causes was 2359 (95% compatibility intervals: 2296-2415) per 100,000 persons when living in non-crowded households. Living in moderately crowded households led to 99 additional deaths (-63 to 256) per 100,000 persons and living in severely crowded households 258 additional deaths (-37 to 607) per 100,000 persons. The effect of crowding on mortality from cardiometabolic diseases, self-harm or substance use was negligible. Interpretation: Excess risk of premature mortality in adolescents living in overcrowded households appears to be small or negligible in Switzerland. Funding: University of Fribourg Scholarship Programme for foreign post-doctoral researchers.

Effect of covering perinatal health-care costs on neonatal outcomes in Switzerland: a quasi-experimental population-based study.

BACKGROUND: Low birthweight and preterm birth are associated with an increased risk of neonatal death and chronic conditions across the life course. Reducing these adverse birth outcomes is a global public health priority and requires strategies to improve health care during pregnancy. We aimed to assess the effect of a Swiss health policy expansion fully covering illness-related costs during pregnancy on health outcomes in newborn babies. METHODS: We implemented a quasi-experimental difference in regression discontinuity design to assess the effect of expansion of Swiss health insurance (on March 1, 2014), to fully cover health-care costs during pregnancy and 8 weeks postpartum, on neonatal outcomes. Before this reform, only costs specific to the standard monitoring of a normal pregnancy were covered. Babies born before March 1, 2014, and their mothers were assigned to the unexposed group, and babies born on or after March 1, 2014, and their mothers were assigned to the exposed group. We included nearly all children born 2011-19 in Switzerland within a period of 9 months around the date March 1, 2014, and control years 2012, 2016, and 2018. Outcomes were birthweight, low birthweight, very low birthweight, gestational age, preterm or extremely preterm birth, and neonatal death. We estimated the intention-to-treat effect of the policy using parametric regression models. FINDINGS: 61 910 children were born 9 months before and 63 991 were born 9 months after March 1, 2014. 382 861 children were born in the same time period around the three control dates. In the period before policy implementation, mean birthweight was 3289 g, gestational age was 275 days, and 6·5% of children had low birthweight, 1·0% very low birthweight, 7·1% were preterm, 0·4% were extremely preterm, and 0·3% died within the first 28 days of life. After initiation of the policy (vs before) mean birthweight increased by 23 g (95% CI 5 to 40) and the predicted proportion of low birthweight births decreased by 0·81% (0·14 to 1·48) and of very low birthweight births decreased by 0·41% (0·17 to 0·65). The effect on very low birthweight was not robust in sensitivity analyses. The policy had a negligible effect on gestational age (mean difference 1 day, 95% CI 0 to 1) and no clear effects on the other examined outcomes. The change in predicted proportion for preterm births was -0·39% (95% CI -1·2 to 0·38), for extremely preterm births was -0·09% (-0·27 to 0·08), and for neonatal death was -0·07% (-0·2 to 0·07). INTERPRETATION: Free access to prenatal care in Switzerland reduced the risk of some adverse health outcomes in newborn babies. Expanding health-care coverage is a relevant health system intervention to reduce the risk of adverse health outcomes in the newborn baby and, potentially, across the life course. FUNDING: Swiss National Science Foundation.

Life-course socioeconomic factors are associated with markers of epigenetic aging in a population-based study.

Adverse socioeconomic circumstances negatively affect the functioning of biological systems, but the underlying mechanisms remain only partially understood. Here, we explore the associations between life-course socioeconomic factors and four markers of epigenetic aging in a population-based setting. We included 684 participants (52 % women, mean age 52.6 ± 15.5 years) from a population and family-based Swiss study. We used nine life-course socioeconomic indicators as the main exposure variables, and four blood-derived, second generation markers of epigenetic aging as the outcome variables (Levine's DNAmPhenoAge, DunedinPoAm38, GrimAge epigenetic age acceleration (EAA), and the mortality risk score (MS)). First, we investigated the associations between socioeconomic indicators and markers of epigenetic aging via mixed-effect linear regression models, adjusting for age, sex, participant's recruitment center, familial structure (random-effect covariate), seasonality of blood sampling, and technical covariates. Second, we implemented counterfactual mediation analysis to investigate life-course and intermediate mechanisms underlying the socioeconomic gradient in epigenetic aging. Effect-size estimates were assessed using regression coefficients and counterfactual mediation parameters, along with their respective 95 % confidence intervals. Individuals reporting a low father's occupation, adverse financial conditions in childhood, a low income, having financial difficulties, or experiencing unfavorable socioeconomic trajectories were epigenetically older and had a higher mortality risk score than their more advantaged counterparts. Specifically, this corresponded to an average increase of 1.1-1.5 years for Levine's epigenetic age (ß and 95 %CI range, ß (minimum and maximum): 1.1-1.5 95 %CI[0.0-0.2; 2.3-3.0]), 1.1-1.5 additional years for GrimAge (ß: 1.1-1.5 95 %CI[0.2-0.6; 1.9-3.0]), a 1-3 % higher DunedinPoAm38 age acceleration (ß: 0.01-0.03 95 %CI[0.00; 0.03-0.04]), and a 10-50 % higher MS score (ß: 0.1-0.4 95 %CI[0.0-0.2; 0.3-0.4]) for the aforementioned socioeconomic indicators. By exploring the life-course mechanisms underlying the socioeconomic gradient in epigenetic aging, we found that both childhood and adulthood socioeconomic factors contributed to epigenetic aging, and that detrimental lifestyle factors mediated the relation between socioeconomic circumstances in adulthood and EAA (31-89 % mediated proportion). This study provides emerging evidence for an association between disadvantaged life-course socioeconomic circumstances and detrimental epigenetic aging patterns, supporting the "sensitive-period" life-course model. Counterfactual mediation analyses further indicated that the effect of socioeconomic factors in adulthood operates through detrimental lifestyle factors, whereas associations involving early-life socioeconomic factors were less clear.

Life course socioeconomic conditions and multimorbidity in old age - A scoping review.

Multimorbidity disproportionally affects individuals exposed to socioeconomic disadvantage. It is, however, unclear how adverse socioeconomic conditions (SEC) at different periods of the life course predict the occurrence of multimorbidity in later life. In this scoping review, we investigate the association between life course SEC and later-life multimorbidity, and assess to which extent it supports different life course causal models (critical period, sensitive period, accumulation, pathway, or social mobility). We identified four studies (25,209 participants) with the first measure of SEC in childhood (before age 18). In these four studies, childhood SEC was associated with multimorbidity in old age, and the associations were partially or fully attenuated upon adjustment for later-life SEC. These results are consistent with the sensitive period and the pathway models. We identified five studies (91,236 participants) with the first measure of SEC in young adulthood (after age 18), and the associations with multimorbidity in old age as well as the effects of adjustment for later-life SEC differed from one study to the other. Among the nine included studies, none tested the social mobility or the accumulation models. In conclusion, SEC in early life could have an effect on multimorbidity, attenuated at least partly by SEC in adulthood.

Intergenerational educational trajectories and premature mortality from chronic diseases: A registry population-based study.

The tracking of educational gradients in mortality across generations could create a long shadow of social inequality, but it remains understudied. We aimed to assess whether intergenerational educational trajectories shape inequalities in early premature mortality from chronic diseases. The study included 544 743 participants of the Swiss National Cohort, a registry population-based study. Individuals were born 1971-1980 and aged 10-19 at the start of the study (1990). Mortality follow-up was until 2018. Educational trajectories were High-High (reference), High-Low, Low-High, Low-Low, corresponding to the sequence of parental-individual attained education. Examined deaths were related to cardiovascular diseases (CVD), cancers, and substance use. Sex-specific inequalities in mortality were quantified via standardized cumulative risk differences/ratios between age 20 and 45. We triangulated findings with a negative outcome control. For women, inequalities were negligible. For men, while inequalities in cancers deaths were negligible, inequalities in CVD mortality were associated to low individual education regardless of parental education. Excess CVD deaths for Low-High were negligible while High-Low provided 234 (95% confidence intervals: 100 to 391) and Low-Low 185 (115 to 251) additional CVD deaths per 100 000 men compared to High-High. That corresponded to risk ratios of 2.7 (1.6 to 4.5) and 2.3 (1.6 to 3.4), respectively. Gradients in substance use mortality were observed only when education changed across parent-offspring. Excess substance use deaths for Low-Low were negligible while High-Low provided 225 (88 to 341) additional and Low-High 80 (23 to 151) fewer substance use deaths per 100 000 men compared to High-High. That corresponded to risk ratios of 1.8 (1.3 to 2.5) and 0.7 (0.5 to 0.9), respectively. Inequalities in premature mortality were driven by individual education and by parental education for some chronic diseases. This could justify the development of intergenerational prevention strategies.

How blood pressure predicts frailty transitions in older adults in a population-based cohort study: a multi-state transition model.

BACKGROUND: Low blood pressure (BP) is associated with frailty in older adults. Our aim was to explore how BP predicts transitions between frailty states. METHODS: We used data from the Lausanne cohort Lc65+, a population-based cohort of older adults randomly drawn from a population registry in Switzerland, in 2004, 2009 and 2014. BP was measured using a clinically validated oscillometric automated device and frailty was defined using Fried's phenotype, every 3 years. We used an illness-death discrete multi-state Markov model to estimate hazard ratios of forward and backward transitions between frailty states (outcome) in relation to BP categories (predictor of interest) with adjustment for sex, age and antihypertensive medication (other predictors). RESULTS: Among 4200 participants aged 65-70 years (58% female) at baseline, 70% were non-frail, 27% pre-frail and 2.0% frail. Over an average follow-up of 5.8 years, 2422 transitions were observed, with 1575 (65%) forward and 847 (35%) backward. Compared with systolic BP (SBP) <130 mmHg, the hazard ratio (95% confidence interval) of the transition from non-frail to pre-frail was 0.86 (0.74 to 1.00) for SBP 130-150 mmHg, and 0.89 (0.74 to 1.06) for SBP ≥150 mmHg. Compared with SBP <130 mmHg, the hazard ratio of the transition from pre-frail to frail was 0.71 (0.50 to 1.01) for SBP 130-150 mmHg, and 0.90 (0.62 to 1.32) for SBP ≥150 mmHg. Diastolic BP was a weaker predictor of forward transitions. CONCLUSIONS: BP categories had no strong relationship with either forward transitions or backward transitions in frailty states. If our findings are confirmed with greater precision and assuming a causal relationship, they would suggest that there is no well-defined optimal BP level to prevent frailty among older adults.

Caesarean section and obesity in young adult offspring: Update of a systematic review with meta-analysis.

As compared with vaginal delivery (VD), caesarean section (CS) birth could be associated with increased risk of obesity in young adult offspring. We aimed to evaluate this association by updating data from a systematic review with meta-analysis of observational studies. From 3774 records identified in PubMed and Embase, we retained six studies and added five studies from the last systematic review, for a total of 11 studies. Crude estimates of the association were retrieved from nine cohort studies (n = 143,869), and maximally adjusted estimates were retrieved from eight cohort studies. Young adults born by CS had higher risk of obesity (body mass index [BMI] ≥ 30 kg/m2 ) than young adults born by VD, corresponding to a crude pooled risk ratio (RR) of 1.30 [95% confidence interval (CI) 1.13 to 1.50] and a maximally adjusted pooled RR of 1.22 [95% CI 1.02 to 1.46]. In a sensitivity analysis pooling, five studies that included maternal prepregnancy BMI, a major potential confounding factor, in the set of controlled covariates, the RR was 1.08 [95% CI 0.92 to 1.27]. We concluded that the association between CS and obesity in young adulthood was mostly explained by confounding from maternal prepregnancy BMI.

Life-course socioeconomic conditions, multimorbidity and polypharmacy in older adults: A retrospective cohort study.

Socioeconomic conditions across the life course may contribute to differences in multimorbidity and polypharmacy in old age. However, whether the risk of multimorbidity changes during ageing and whether life-course socioeconomic conditions are associated with polypharmacy remain unclear. We investigated whether disadvantaged childhood socioeconomic conditions (CSCs) predict increased odds of multimorbidity and polypharmacy in older adults, whether CSCs remain associated when adjusting for adulthood socioeconomic conditions (ACSs), and whether CSCs and ACSs are associated cumulatively over the life course. We used data for 31,432 participants (multimorbidity cohort, mean [SD] age 66·2[9] years), and 21,794 participants (polypharmacy cohort, mean age 69·0[8.9] years) from the Survey of Health, Ageing, and Retirement in Europe (age range 50-96 years). We used mixed-effects logistic regression to assess the associations of CSCs, ASCs, and a life-course socioeconomic conditions score (0-8; 8, most advantaged) with multimorbidity (≥2 chronic conditions) and polypharmacy (≥5 drugs taken daily). We found an association between CSCs and multimorbidity (reference: most disadvantaged; disadvantaged: odds ratio (OR) = 0·79, 95% confidence interval (CI) 0·70-0·90; middle: OR = 0·60; 95%CI 0·53-0·68; advantaged: OR = 0·52, 95%CI 0·45-0·60, most advantaged: OR = 0·40, 95%CI 0·34-0·48) but not polypharmacy. This multimorbidity association was attenuated but remained significant after adjusting for ASCs. The life-course socioeconomic conditions score was associated with multimorbidity and polypharmacy. We did not find an association between CSCs, life-course socioeconomic conditions, and change in odds of multimorbidity and polypharmacy with ageing. Exposure to disadvantaged socioeconomic conditions in childhood or over the entire life-course could predict multimorbidity in older age.